Chagas' Disease
Trypanosomal diseases include some of the most pervasive and problematic illnesses facing man today. Of these, Chagas' disease (American trypanosomiasis), which is concentrated principally in Central and South America, is of particular concern, both for the number of individuals infected and for the lack of adequate chemotherapy to treat the disease (Brener, Z., Bull. WHO 60:463-473 (1982); Hammond et al., Trans. Royal Soc'y Trop. Med. Hyg. 78:91-95 (1984)). In adults, the chronic form of Chagas' disease results in cardiomyopathy, megaesophagus, megacolon and death. (Webster, L., Chapter 43 in Goodman and Gilman's the Pharmaceutical Basis of Therapeutics, Gilman, A., et al., eds., 8th Ed., p. 1008, Pergamon Press, New York (1990)).
Although estimates of the extent of Chagas' disease vary, it is generally agreed that from 10 to 20 million people are presently infected, representing in some reporting areas up to 43% of the total population. (Kolberg, R., Science 264:1859-1861 (1994)). While the causative agent for Chagas' disease, Trypanosoma cruzi, is transmitted predominantly in rural areas by the reduviid bug, the disease is finding its way into urban areas through blood transfusion (Brener, A., Pharmacol. Ther. 7:71-90 (1979)). Chagas' disease is not presently considered to be a significant problem in North America, with only a few cases of indigenous Chagas' disease having been reported in the United States. (See, e.g., Schiffler, R. J., et al., JAMA 251:2983-2984 (1984)). However, T. cruzi is found in mammals and insects across the southern United States, as far north as Virginia (Downs, W. G., J. Parasit. 49:50 (1963)).
Although two agents which abolish parasitemia in the acute phase are presently available (Nifurtimox (3-methyl-4-(5-nitrofurfurylidineamino) tetrahydro-4H-1,4-thiazine-1,1-dioxide)and Benznidazole(N-benzyl-2-nitro-1-imidazoleacetamide); Keierszenbaum, F., in Trop. Med. Parasit., Mansfield, ed., Marcel Dekker, New York (1984)), neither results in a complete cure and both have serious side effects. Because of toxicity and the inability to completely abolish parasitemia with certainty, these drugs are recommended as treatments for individuals with chronic Chagas' disease only because of the seriousness of the disease and the lack of superior drugs. (Webster, L., Chapter 43 in Goodman and Gilman's the Pharmaceutical Basis of Therapeutics, Gilman, A., et al., eds., 8th Ed., p. 1011, Pergamon Press, New York (1990)). The unavailability of adequate chemotherapeutic agents for the treatment of chronic Chagas' disease underlies the need for new antichagasic drugs.